A comprehensive analysis concerning eating behavior associated with chronic diseases among Romanian community nurses.

Introduction: Lifestyle factors, including inadequate eating patterns, emerge as a critical determinant of chronic disease. Apart from caring for patients, nurses should also take an active role in monitoring and managing their own health. Understanding the intricate relationship between nurses' eating behavior and managing their own health is crucial for fostering a holistic approach to healthcare, therefore our study aimed to evaluate eating behavior and demographic factors influencing chronic disease prevalence in a sample of community nurses from Romania. Methods: Between October-November 2023, 1920 community nurses were invited to answer an online survey, using an advertisement in their professional network. Of them, 788 responded. In the survey, which included a semi-quantitative food frequency questionnaire with 53 food items, the Intuitive Eating Survey 2 (IES-2), and demographic items were used. Results: A multivariate model was built for the prediction of the association between eating behavior and other factors associated with chronic diseases. The majority of participants were females (95.1%), with the largest age group falling between 40 and 49.9 years (48.2%). Regarding the EFSA criteria for adequate carbohydrate and fat intake, 20.2% of the group have a high intake of carbohydrates, respectively, 43.4% of the group have a high intake of fat. Analysis of chronic diseases indicated that 24.9% of individuals reported at least one diagnosis by a physician. The presence of chronic disease was associated with a low level of perceived health status, with an OR = 3.388, 95%CI (1.684-6.814), compared to those reporting excellent or very good perceived health status. High stress had an OR = 1.483, 95%CI (1.033-2.129). BMI had an OR = 1.069, 95%CI (1.032-1.108), while low carbohydrate diet score had an OR = 0.956, 95%CI (0.920-0.992). Gender and IES-2 did not significantly contribute to the model, but their effect was controlled. Discussion: By unraveling the intricate interplay between nutrition, lifestyle, and health outcomes in this healthcare cohort, our findings contribute valuable insights for the development of targeted interventions and support programs tailored to enhance the well-being of community nurses and, by extension, the patients they support.

The Implications of Cytochrome P450 2D6/CYP2D6 Polymorphism in the Therapeutic Response of Atypical Antipsychotics in Adolescents with Psychosis-A Prospective Study.

BACKGROUND: The plasma level of antipsychotics and their metabolites depends on the activity of the cytochrome P450 (CYP) system in the liver. This research aims to test the individual response variability to atypical antipsychotic drugs, depending on the activity of the CYP2D6 enzyme. METHODS: In a prospective, noninterventional study, we included 56 adolescents, 51.79% male, diagnosed with schizophrenia. The patients underwent DNA sampling for genotyping SNP by RT-PCR and CYP* allelic variants using Applied Bio-systems™ TaqMan® Assays Foster City, CA, USA). and clinical and paraclinical assessments. The effectiveness of the therapy was evaluated with the PANSS scores at baseline and 3, 6, and 12 months after the initiation of an atypical antipsychotic treatment. RESULTS: Based on the genotyping results, the patients were divided into slow metabolizers (Group 1), extensive metabolizers (Group 2), and intermediate metabolizers (Group 3). The PANSS score showed a significant decrease in Group 2, compared to Group 3 after 3 (p = 0.02), 6 (p = 0.0009), and 12 months (p < 0.0001). The patients in Group 1 showed high PANSS scores, and those in Group 2 had fewer adverse reactions than the other groups. CONCLUSIONS: Assessing the CYP2D6 polymorphism may be useful in clinical pediatric psychiatric practice towards improving clinical results and patients' quality of life.

Polyurethane Microstructures for 2'-Deoxycytidinic Acid Delivery: Preparation and Preliminary Characterization.

Background and Objectives: Nucleotide delivery has emerged as a noteworthy research trend in recent years because of its potential utility in addressing a range of genetic defects resulting in the presence of incorrect nucleotides. The primary goals of this research were to create and to characterize polyurethane microstructures, with the aim of utilizing them for nucleotide transport. Materials and Methods: Two samples were prepared using an aliphatic diisocyanate in reaction with a mixture of polyethylene glycol and polycaprolactone diol, where 2'-deoxycytidinic acid was used as the active agent and glycerol 1,2-diacetate was used as an enhancer of the aqueous solubility. The solubility, pH, size distribution, and surface charge of the samples were measured, and encapsulation efficacy and release, cell proliferation, and irritation tests on mouse skin were conducted. Results: The results showed almost neutral acidic-basic structures with a high heterogeneity, and a medium tendency to form clusters with non-cytotoxic and non-irritative potentials. Conclusions: Future research could explore the efficacy of this carrier in delivering other nucleotides, as well as investigating the long-term effects and safety of these microstructures in vivo.

Genetic Characterization of Dilated Cardiomyopathy in Romanian Adult Patients.

Dilated cardiomyopathy (DCM) represents a group of disorders affecting the structure and function of the heart muscle, leading to a high risk of heart failure and sudden cardiac death (SCD). DCM frequently involves an underlying genetic etiology. Genetic testing is valuable for risk stratification, treatment decisions, and family screening. Romanian population data on the genetic etiology of DCM are lacking. We aimed to investigate the genetic causes for DCM among Romanian adult patients at tertiary referral centers across the country. Clinical and genetic investigations were performed on adult patients presenting to tertiary hospitals in Romania. The genetic investigations used next-generation sequencing panels of disease-associated DCM genes. A total of 122 patients with DCM underwent genetic testing. The mean age at DCM diagnosis was 41.6 ± 12.4 years. The genetic investigations identified pathogenic or likely pathogenic variants in 50.8% of participants, while 25.4% had variants of unknown significance. Disease-causing variants in 15 genes were identified in people with DCM, with 31 previously unreported variants. Variants in TTN, LMNA, and DSP explained 75% of genetic causes for DCM. In total, 52.4% of patients had a family history of DCM/SCD. Left ventricular ejection fraction of <35% was observed in 41.9% of patients with disease-causing variants and 55% with negative or uncertain findings. Further genotype-phenotype correlations were explored in this study population. The substantial percentage (50.8%) of disease-causing variants identified in patients with DCM acknowledges the importance of genetic investigations. This study highlights the genetic landscape in genes associated with DCM in the Romanian population.

When Mast Cells Run Amok: A Comprehensive Review and Case Study on Severe Neonatal Diffuse Cutaneous Mastocytosis.

Neonatal diffuse cutaneous mastocytosis (NDCM) is defined as the infiltration of the epidermis by a clonal proliferation of mast cells, observed at birth, without initial signs of systemic involvement. The typical driver mutation is in the KIT gene. We report a rare case of a boy, born at term, already presenting at birth with generalized subcutaneous nodules on the face, scalp, trunk, back, hands, and feet. The spleen, liver, and inflammatory markers were normal at birth. Tryptase was significantly elevated. A bone marrow biopsy showed no mast cell involvement at age 2 months. A punch biopsy at age 2 months revealed CD117-positive cells diffusely infiltrating the skin, with subsequent DNA NGS sequencing for the formalin-fixed paraffin embedded tissue (FFPE) identifying the pathogenic NM_000222.3:c.1504_1509dup; p.(Ala502_Tyr503dup) variant in the KIT gene previously associated with cutaneous mastocytosis. At 2 years follow-up, he had splenomegaly and multiple cervical and inguinal adenopathy, while the skin nodules persisted, especially on the scalp with accompanying pruritus. He received oral and local sodium cromoglycate, oral antihistamines, antibiotic cream for skin infection, and iron supplementation; however, compliance to treatment was relatively low. The prognosis is difficult to predict, as he developed systemic involvement, failure to thrive, and mild psychomotor delay. A case aggregation of NDCM reported in the literature was performed to provide a comprehensive overview of this rare pathology, to better understand the prognosis. NDCM is a life-threatening disease with severe complications. Almost half had severe complications, such as mast hepatosplenomegaly, adenopathy, bacterial infections, mast cell leukaemia, and systemic involvement.

The impact of theory of mind, stress and professional experience on empathy in Romanian community nurses-a cross-sectional study.

BACKGROUND: High empathy levels in health professionals represent an important factor in patient satisfaction and compliance, reducing patient anxiety and pain, enhancing diagnostic and clinical results and strengthening patient empowerment. Our purpose was to determine empathy level and to identify which of the socioeconomic status (SES) and psychological factors were able to predict highest empathy levels in a Romanian sample of community nurses. METHODS: Community nurses were invited in January-February 2023 to provide an answer to an online survey, using an advertisement in a professional network. 1580 participants voluntarily agreed to take part in this study, with a response rate of 85.8%. The survey included the Toronto Empathy Questionnaire, the Reading the Mind in the Eyes Test and socio-economic status items. A multivariate model for the prediction of belonging to the highest quartile of empathy as opposed to lowest quartile was constructed using SES and psychological variables as factors. RESULTS: The mean (SD) empathy level was 49.1 (6.7), with 74.7% of participants over the threshold of high empathy level. In the multivariate analysis, predictors of belonging to the highest quartile of TEQ, as opposed to the lowest quartile were: low self-perceived stress level (OR = 2.098, 95%CI 1.362-3.231), higher experience as a community nurse (OR = 1.561, 95%CI 1.120-2.175) and higher levels of the theory of mind (OR = 1.158, 95%CI 1.118-1.199), when controlling for gender, age, relationship status, presence of children in families, education, and income. CONCLUSIONS: Training programs targeting to increase emotional competences, reduce levels of stress and encourage personnel retention have the potential to increase the quality of community nursing in Romania.

Predictors of Changes in Quality of Life of Patients with Major Depressive Disorder-A Prospective Naturalistic 3-Month Follow-Up Study.

Major depressive disorder (MDD) is one of the leading causes of disease burden worldwide and affected patients frequently report impairments in quality of life (QoL). Therefore, the present research aimed to identify predictors of domain-specific QoL changes in MDD patients following the acute phase of pharmacological treatment (3-month). This study is a prospective, naturalistic, and observational analysis on 150 patients. Depressive symptoms, QoL, overall pain intensity, and functionality were assessed using Hamilton Depression Rating Scale, World Health Organization Quality of Life scale-abbreviated version, Visual Analog Scale, and Sheehan Disability Scale, respectively. Reductions in symptom severity and disability were predictors of improvement across all domains of QoL. Pain intensity reduction was a predictor of increases in the physical aspect of QoL. A reduced number of psychiatric hospitalizations and being in a relationship predicted an improvement of QoL in the psychological domain whereas a positive history of suicidal attempts was associated with better social relationships QoL. The predictive models explained 41.2% and 54.7% of the variance in psychological and physical health domains of QoL, respectively. Awareness of sociodemographic and changes in clinical factors that impact the change in domain-specific QoL might help in shaping personalized treatment.

An SI3-σ arch stabilizes cyanobacteria transcription initiation complex.

Multisubunit RNA polymerases (RNAPs) associate with initiation factors (σ in bacteria) to start transcription. The σ factors are responsible for recognizing and unwinding promoter DNA in all bacterial RNAPs. Here, we report two cryo-EM structures of cyanobacterial transcription initiation complexes at near-atomic resolutions. The structures show that cyanobacterial RNAP forms an "SI3-σ" arch interaction between domain 2 of σA (σ2) and sequence insertion 3 (SI3) in the mobile catalytic domain Trigger Loop (TL). The "SI3-σ" arch facilitates transcription initiation from promoters of different classes through sealing the main cleft and thereby stabilizing the RNAP-promoter DNA open complex. Disruption of the "SI3-σ" arch disturbs cyanobacteria growth and stress response. Our study reports the structure of cyanobacterial RNAP and a unique mechanism for its transcription initiation. Our data suggest functional plasticity of SI3 and provide the foundation for further research into cyanobacterial and chloroplast transcription.

COVID-19-Associated Acute Psychotic Disorder-Longitudinal Case Report and Brief Review of Literature.

Even though since the beginning of the COVID-19 pandemic, the literature became more and more abundant on data and hypotheses about the various consequences on people's lives, more clarity needs to be added to the existing information. Besides the stressful experiences related to the COVID-19 pandemic, SARS-CoV-2 infection has been proven to impact brain functioning through direct and indirect pathogenic mechanisms. In this context, we report a case of a patient presenting with a first episode of psychosis following COVID-19. In our case, a 28-year-old male patient with no personal or family psychiatric history developed psychotic symptoms (delusions, hallucinations, and disorganized behaviour) that required antipsychotic treatment and inpatient hospitalization one week after he was discharged from the hospital after COVID-19. At the six-month and one-year follow-up, the patient was in remission without any psychotic signs or symptoms. A brief review of the literature is also provided. The case presented in this article outlines the possibility that the post-COVD-19 recovery period might be a crucial time for the onset of acute psychotic disorder, and therefore, routine psychiatric assessments should be carried out during all phases of the disease. A clearer picture of the impact of the COVID-19 pandemic on mental health will most likely be revealed in the future as many consequences need long-term evaluation.

Copy number variation analysis in 189 Romanian patients with global developmental delay/intellectual disability.

BACKGROUND: Developmental delay and intellectual disability represent a common pathology in general population, involving about 3% of the pediatric age population, the genetic etiology being often involved. The aim of this study was to determine the clinically relevant copy number variants in patients diagnosed with global developmental delay/intellectual disability in our population, using the chromosomal microarray analysis. METHODS: We analyzed 189 patients diagnosed with global developmental delay/intellectual disability, presented in Clinical Emergency Hospital for Children, Cluj-Napoca. The patients were completely clinically investigated, including dysmorphic and internal malformations evaluation, psychiatric, neuropsychological and metabolic evaluation, standard karyotyping. Genomic analysis was done using chromosomal microarray analysis. RESULTS: Pathogenic findings (including uniparental disomy) and variants of unknown significance were detected in 53 of 189 patients (28.04%). Pathogenic copy number variants and uniparental disomy were observed in 35 of 189 patients (18.51%). Two patients presented uniparental disomy for chromosome 15, one with clinical phenotype of Prader-Willi syndrome and the other with clinical phenotype with Angelman syndrome. Within the category of pathogenic findings, the recurrent copy number variants were seen in 21 of 35 patients (60%). CONCLUSIONS: The increased percentage of pathogenic structural variants observed in patients with global developmental delay/intellectual disability analyzed by chromosomal microarray technique supports its use in patients with a non-specific phenotype such as these neurodevelopmental disorders. The high percentage of recurrent pathogenic variants between these findings is a finding that support their initial evaluation when a genetic testing algorithm could be a useful option.

Preliminary Analysis of the Glycolipid Profile in Secondary Brain Tumors.

Glycosphingolipids (GSLs) play numerous roles in cellular processes, including cell proliferation, apoptosis, inflammation, and cell signaling. Alteration of the GSLs metabolism leads to the accumulation of particular species of GSLs, which can lead to various pathologies, including carcinogenesis and metastasis; in essence, all neoplasms are characterized by the synthesis and aberrant organization of GSLs expressed on the cell surface. Secondary brain tumors make up the majority of intracranial cancers and generally present an unfavorable prognosis. In the present work, a native GSL mixture extracted and purified from a secondary brain tumor with primary pulmonary origin was obtained through extraction and purification and analyzed by MALDI TOF mass spectrometry. Research in the field of lipidomics could offer new data for the understanding of brain tropism and metastatic pathways, by studying the glycolipid molecules involved in the process of metastasis in general and in the production of brain metastases in particular. This could shed new light on the pattern of lipid glycosylation in secondary brain tumors, with a great impact on the effectiveness of cancer therapies, which could be adapted to the specific molecular pattern of the tumor.

Current Perspectives on Pharmacological and Non-Pharmacological Interventions for the Inflammatory Mechanism of Unipolar Depression.

Since depression remains a major public health issue there is a constant need for new and more efficient therapeutic strategies based on the mechanisms involved in the aetiology of depression. Thus, the pathogenic link between depression and inflammation is considered to play a potential key role in the development of such therapies. This review summarizes the results of various pharmacological (non-steroidal anti-inflammatory drugs, aspirin, cyclooxygenase inhibitors, cytokine inhibitors, corticosteroids, statins, minocycline, N-acetyl cysteine, omega-3 fatty acids and probiotics) and non-pharmacological interventions (electroconvulsive therapy, physical exercise and psychological therapy) and outlines their efficacy and discusses potential challenges. Both conventional and non-conventional anti-inflammatory drugs showed promising results according to the specific group of patients. The pre-existing pro-inflammatory status was, in most cases, a predictor for clinical efficacy and, in some cases, a correlation between clinical improvement and changes in various biomarkers was found. Some of the non-pharmacological interventions (physical exercise and electroconvulsive therapy) have also showed beneficial effects for depressive patients with elevated inflammatory markers. Treatments with anti-inflammatory action may improve clinical outcomes in depression, at least for some categories of patients, thus opening the way for a future personalised approach to patients with unipolar depression regarding the inflammation-related mechanism.

The Impact of the COVID-19 Pandemic on Inpatient Admissions for Psychotic and Affective Disorders: The Experience of a Large Psychiatric Teaching Hospital in Romania.

The COVID-19 pandemic resulted in a global sanitary crisis and, in addition, elicited serious mental health consequences. The utilization of psychiatric hospital-based services acts as an indicator of public mental health. Therefore, this research sought to investigate differences in the numbers and characteristics of inpatient admissions for psychotic and affective disorders at the largest Romanian psychiatric hospital between the period of lockdown (16 March−15 May 2020) and another three corresponding periods: the same year in the pre-lockdown period (16 January−15 March 2020), the immediate post-lockdown period (16 May−15 July 2020), and two years later (16 March−15 May 2022). A retrospective analysis was performed. The study included a total of 6604 patients. Inpatient admissions decreased during lockdown in comparison with the pre-lockdown period and immediate post-lockdown period for psychotic disorders (p < 0.001 and p < 0.001, respectively) and affective disorders (p < 0.001 and p < 0.001, respectively). For both psychotic and affective disorders, a decrease in the age of the patients admitted during lockdown, as compared with the pre-lockdown period (p < 0.05 and p < 0.001, respectively), was observed. The length of the hospital stay for affective disorders was higher immediately post-lockdown in comparison with the lockdown period (p < 0.001). Collectively, the present findings provide a glimpse of the immediate and long-term consequences of the COVID-19 pandemic and lockdown measures on patients' access to mental healthcare in the form of hospitalization, and these findings could provide the basis for the development of a different approach to times of crisis.

Psychosis Associated with Acquired Porencephaly-Cause or Incidental Finding? Case Report and Review of Literature.

Porencephaly, a rare disease affecting the central nervous system, is represented by a cerebrospinal fluid-filled cavity in the brain. There are two types of porencephalic cavities: congenital and acquired. Porencephaly is mainly associated with neurological and developmental consequences. Associated psychotic symptoms were reported in a few cases, and due to this fact, there is a knowledge gap regarding the diagnostic and therapeutic approach to such cases. We present the case of a 32-year-old male diagnosed with a psychotic disorder associated with acquired porencephaly. The porencephalic cystic lesions were most probably due to a traumatic brain injury at the age of 6 years old. The psychotic symptomatology consisted of interoceptive/visceral hallucinations, delusions with persecutory and religious/magic content and disorganised behaviour. The porencephalic cavity was confirmed by a computed tomography scan. The patient was treated over the course of time with risperidone, olanzapine and zuclopenthixol. The existing literature regarding other cases of psychosis associated with porencephaly is discussed. In conclusion, even though porencephaly was asymptomatic for a long period of time, we argue that there is a causal relationship between the chronic psychotic symptoms and the porencephalic cyst in our case.

Case Report: Novel Biallelic Variants in DNAJC21 Causing an Inherited Bone Marrow Failure Spectrum Phenotype: An Odyssey to Diagnosis.

Bone marrow failure represents an umbrella diagnosis for several life-threatening disorders. In many people, the etiology remains unknown for a long time, leading to an odyssey to diagnosis, with numerous tests performed and sometimes inappropriate treatment. Biallelic pathogenic variants in the DNAJC21 gene were recently discovered to cause bone marrow failure syndrome type 3, having phenotypic overlap with Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, and Diamond-Blackfan anemia. Herein, we report an 8-year-old boy, with normal intellect, presenting bone marrow failure; growth retardation; failure to thrive; recurrent infections (including sepsis); cryptorchidia; skeletal, skin, teeth, and hair abnormalities; joint hypermobility; eczema; palpebral ptosis; high myopia; rod-cone retinal dystrophy; and short telomeres. He underwent several tests and evaluations, including genetic investigations (panel and exome sequencing), before the DNAJC21 gene was known to cause disease. Whole-genome sequencing performed at the age of 7 years, identified two novel, pathogenic, and compound heterozygous variants in the DNAJC21 gene: NM_001012339.3:c.148C>T (stopgain-maternal origin), p.Gln50∗ and c.643_644delinsTTT (frameshift paternal origin), and p.Lys215Phefs∗71. He received aggressive treatments for his multisystem disease: blood cell transfusions, high-dose corticosteroids, immunoglobulins, multiple antibiotics, vitamins, growth hormone, and others. However, allogeneic hematopoietic stem cell transplantation was avoided. The clinical evolution of bone marrow failure and recurrent infections stabilized with age, yet the myopia progressed. Exocrine pancreatic insufficiency was not detected. This report widens the molecular and clinical understanding of bone marrow failure syndrome type 3. Genome sequencing directed a precise diagnosis that improved patient management and enabled family genetic counseling.

In Vitro Fertilization Using Preimplantation Genetic Testing in a Romanian Couple Carrier of Mutations in the TTN Gene: A Case Report and Literature Review.

Severe congenital myopathy with fatal cardiomyopathy (EOMFC) is a rare genetic neuromuscular disorder inherited in an autosomal recessive manner. Here we presented a successful pregnancy obtained by in vitro fertilization (IVF) using preimplantation genetic testing (PGT) in one young Romanian carrier couple that already lost mutation(s) within the TNN gene and whose first baby passed away due to multiple complications. It was delivered via emergency C-section at 36 weeks and fully dependent on artificial ventilation for a couple of months, weighing 2200 g and an APGAR score of 3. The aCGH + SNP analysis revealed an abnormal profile of the first newborn; three areas associated with loss of heterozygosity on chromosome 1 (q25.1-q25.3) of 6115 kb, 5 (p15.2-p15.1) of 2589 kb and 8 (q11.21-q11.23) of 4830 kb, a duplication of 1104 kb on chromosome 10 in the position q11.22, and duplication of 1193 kb on chromosome 16 in the position p11.2p11.1. Subsequently, we proceeded to test the parents and showed that both parents are carriers; confirmed by Sanger and NGS sequencing-father-on Chr2(GRCh37):g.179396832_179396833del-TTN variant c.104509_104510del p.(Leu34837Glufs*12)-exon 358 and mother-on Chr2(GRCh37):g.179479653G>C-TTN variant c.48681C>G p.(Tyr16227*)-exon 260. Their first child died shortly after birth due to multiple organ failures, possessing both parent's mutations; weighing 2200 g at birth and received an APGAR score of 3 following premature delivery via emergency C-section at 36 weeks. Two embryos were obtained following the IVF protocol; one possessed the mother's mutation, and the other had no mutations and was normal (WT). In contrast with the first birth, the second one was uneventful. A healthy female baby weighing 2990 g was delivered by C-section at 38 weeks, receiving an APGAR score of 9.

Mini-Review Regarding the Applicability of Genome Editing Techniques Developed for Studying Infertility.

Infertility is a highly debated topic today. It has been long hypothesized that infertility has an idiopathic cause, but recent studies demonstrated the existence of a genetic substrate. Fortunately, the methods of editing the human genome proven to be revolutionary. Following research conducted, we identified a total of 21 relevant studies; 14 were performed on mice, 5 on zebrafish and 2 on rats. We concluded that over forty-four genes in total are dispensable for fertility in both sexes without affecting host homeostasis. However, there are genes whose loss-of-function induces moderate to severe phenotypic changes in both sexes. There were situations in which the authors reported infertility, exhibited by the experimental model, or other pathologies such as cryptorchidism, cataracts, or reduced motor activity. Overall, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 are techniques that offer a wide range of possibilities for studying infertility, even to create mutant variants. It can be concluded that ZFNs, TALENs, and CRISPR/Cas9 are crucial tools in biomedical research.

Biallelic variants in BRCA1 gene cause a recognisable phenotype within chromosomal instability syndromes reframed as BRCA1 deficiency.

Pathogenic variants in BRCA1 gene in heterozygous state are known to be associated with breast-ovarian cancer susceptibility; however, biallelic variants cause a phenotype recognised as Fanconi anaemia complementation group S. Due to its rarity, medical management and preventive screening measures are insufficiently understood. Here, we present nine individuals (one new and eight previously presented) with biallelic variants in BRCA1 gene, to delineate clinical features in comparison with other chromosome instability syndromes and understand the patients' health risk. Features seen in these 9 individuals (7 females/2 males) include prenatal and postnatal growth failure (9/9), microcephaly (9/9), hypo/hyperpigmented lesions (9/9), facial dysmorphism (9/9), mild developmental delay (8/9) and early-onset solid tumours (5/9). None presented bone marrow failure or immunodeficiency. Individuals with biallelic variants in BRCA1 also showed chromosomal instability by mitomycin and diepoxybutane test. The phenotype caused by biallelic BRCA1 variants is best framed between Fanconi anaemia and Nijmegen syndrome, yet distinct due to lack of bone marrow failure and immunodeficiency. We hypothesise that disease class should be reframed and medical management in people with biallelic variants in BRCA1 should emphasise on detection of solid tumour development and avoiding exposure to ionising radiation.

Cardiofaciocutaneous syndrome - a longitudinal study of a case over 33 years: case report and review of the literature.

Cardiofaciocutaneous (CFC) syndrome [Online Mendelian Inheritance in Man (OMIM) #115150] is characterized by craniofacial dysmorphism, heart malformation, ectodermal abnormalities, neuromotor delay and intellectual disability. It is not a frequent disease, about 300 cases have been reported in the medical literature. We describe the case of a 34-year-old patient presenting with CFC syndrome phenotype, monitored since the age of 1 1∕2 years. Clinical findings included craniofacial dysmorphism, development delay, heart malformation and severe intellectual disability. The evolution was with progressive intellectual disability, hypogonadism, hypertrophic cardiomyopathy, wrinkled palms and soles. Molecular analysis showed a heterozygous variant in the B-Raf proto-oncogene, serine∕threonine kinase (BRAF) gene (7q34): NM_001354609.2:c.1502A>G, with pathogenic significance. We report this case, observed along a period of 33 years, for illustration of clinical evolutive particularities, and for difficulties in establishing the positive diagnosis.

CHDH-PNPLA3 Gene-Gene Interactions Predict Insulin Resistance in Children with Obesity.

INTRODUCTION: Insulin resistance plays a major role in metabolic syndrome and is recognized as the most common risk factor for non-alcoholic fatty liver disease (NAFLD). Identifying predictors for insulin resistance could optimize screening and prevention. PURPOSE: To evaluate the contribution of multiple single nucleotide polymorphisms across genes related to NAFLD and choline metabolism, in predicting insulin resistance in children with obesity. METHODS: One hundred fifty-three children with obesity (73 girls), aged 7-18 years, were evaluated within the NutriGen Study (ClinicalTrials.gov-NCT02837367). Insulin resistance was defined by Homeostatic Model Assessment for insulin-resistance cut-offs that accommodated pubertal and gender differences. Anthropometric, metabolic, intake-related variables, and 55 single nucleotide polymorphisms related to NAFLD and choline metabolism were evaluated. Gene-gene interaction effects were assessed using Multiple Data Reduction Software. RESULTS: Sixty percent (93/153) of participants showed insulin resistance (58.7% of boys, 63% of girls). Children with insulin resistance presented significantly higher values for standardized body mass index, triglycerides, transaminases and plasma choline when compared to those without insulin resistance. Out of 52 single nucleotide polymorphisms analysed, the interaction between genotypes CHDH(rs12676) and PNPLA3(rs738409) predicted insulin resistance. The model presented a 6/10 cross-validation consistency and 0.58 testing accuracy. Plasma choline levels and alanine aminotransferase modulated the gene interaction effect, significantly improving the model. CONCLUSION: The interaction between genotypes in CHDH and PNPLA3 genes, modulated by choline and alanine aminotransferase levels, predicted insulin-resistance status in children with obesity. If replicated in larger cohorts, these findings could help identify metabolic risk in children with obesity.